Sleep Electroencephalographic Spectral Power After Withdrawal from Alcohol in Alcohol-Dependent Patients Bernd Feige, Susanne Scaal, Magdolna Hornyak, Horst Gann, and Dieter Riemann Background: Dysfunctional hyperarousal is suspected to be a neurophysiological determinant of relapse in abstinent alcohol-dependent patients. In the present study, we used spectral power analysis of the sleep electroencephalographic (EEG) to quantify brain activity during sleep in patients during subacute withdrawal as well as in control subjects. Our hypothesis was that the subgroup of patients who relapsed within the 3 months to follow-up would exhibit-increased dysfunctional arousal man- ifested by higher-frequency (b) EEG power during sleep. Methods: Twenty-six alcohol-dependent in-patients were examined with polysomnography over 2 nights 2 to 3 weeks after withdrawal. At the 3-month clinical follow-up assessment, 12 of them had relapsed and 14 abstained. The control group consisted of 23 healthy subjects similar to the patients with alcohol dependence in age and gender distribution. Spectral sleep EEG analysis was performed on both nights (adaptation and baseline) of all subjects. Logarithmic artifact-controlled spectral band power of sleep stage 2 and rapid eye movement (REM) sleep was analyzed for Group, Gender, and Age effects using multiple analyses of covariance. Three groups were compared with the Group factor: relapsers, abstainers, and controls. Results: Generally, both Group and Age effects were significant for the second, baseline night for the visually scored sleep parameters, while spectral EEG parameters showed significant differences in the adaptation night. In the adaptation night, a significant enhancement in the b2 band (24–32 Hz) was seen in REM sleep in relapsers relative to both abstainers and controls. Conclusions: The b2 increase could be interpreted as a sign of dysfunctional arousal during REM sleep ‘‘unmasked’’ by the additional stressor of sleep environment adaptation. Its determinants are likely to be both premorbid and drinking history related. Key Words: Human, Sleep, EEG Spectral Effects, Alcohol Dependence, Relapse. A BOUT HALF OF all alcohol-dependent patients relapse within 3 months after withdrawal (Marlatt and Gordon, 1985). Therefore, it is important to under- stand the conditions that promote or prevent relapse as precisely as possible. Besides psychosocial factors, there is strong evidence that neurophysiological markers are important for both the development of addiction and for the process of relapse. Several weeks after acute withdrawal, patients are still characterized by increased restlessness, memory and con- centration deficits, and general cognitive impairment. (Mann et al., 1999) have shown in a longitudinal study that some aspects of cognitive impairment (particularly in verbal short-term memory) persist for at least 6 weeks after acute withdrawal. This ‘‘protracted alcohol withdrawal syndrome’’ (Bokstro¨m and Balldin, 1992; Kissin, 1979) is regarded as a major factor for relapse (Parsons et al., 1987; Schuckit et al., 1987; Tarter and Ryan, 1983). Waking electroencephalographic (EEG) markers have been used to assess both the acute effects of alcohol (Cohen et al., 1993; Porjesz and Begleiter, 1975) and the protracted alcohol withdrawal syndrome (Kaplan et al., 1985). Kaplan et al. (1985) also noticed an increased amount of higher-frequency (i.e., b) EEG activity that decreased over time after detoxification. The amount of b activity was recently found to be related to genetic vari- ations in a GABAa receptor locus (Porjesz et al., 2002) and was shown to correlate with behavioral hyperarousal (Bauer and Hesselbrock, 1993; in sleep: Nofzinger et al., 2000). Event-related potential studies during protracted withdrawal also showed signs of increased cortical excit- ability correlating with the severity of alcoholism (Olbrich et al., 2002). Therefore, dysfunctional excitability and hyperarousal can be seen as important factors for both development and maintenance of alcohol addiction. Sleep disturbances observed in alcohol-dependent patients constitute a second group of neurophysiological markers that are possibly important for the initial devel- opment of addiction (Wong et al., 2004), its maintenance, and relapse after withdrawal. Such disturbances are From the Department of Psychiatry and Psychotherapy, University of Freiburg, Freiburg, Germany. Received for publication June 16, 2006; accepted August 30, 2006. This study was supported by the German Ministry for Education and Research (BMBF; FKZ 01 EB 9413). Reprint requests: Dr. Bernd Feige, Department of Psychiatry and Psychotherapy, Hauptstrae 5, Freiburg 79104, Germany; Fax: 149-761-270-6619; E-Mail: Bernd.Feige@gmx.net Copyright r 2006 by the Research Society on Alcoholism. DOI: 10.1111/j.1530-0277.2006.00260.x Alcohol Clin Exp Res, Vol 31, No 1, 2007: pp 19–27 19 ALCOHOLISM:CLINICAL AND EXPERIMENTAL RESEARCH Vol. 31, No. 1 January 2007